A rapid decline in research and development of new antibiotics coincides with increasing frequency of infections caused by multi-drug-resistant pathogens. The key reason of bacterial resistance is the indiscriminate use of antibiotics (Zunita et al., 2008). The outbreak of methicillin-resistant Staphylococcus aureus (MRSA), occurred over fifty years ago (Habte-Gabr et al., 2010), and is now widespread throughout the world. S. aureus is the most common bacterial pathogen, which causes skin, soft-tissue, and endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, and sepsis (David et al., 2010). MRSA has now mutated for decades with increasing incidence of community associated (CA) infections, often producing painful pus filled lesions of deep tissues (Kumar et al., 2010).
In Europe mortality rates due to hospital acquired infections by resistant bacteria has exceeded more than 25,000 annually (World Health Organization 2012). In 2005, a report submitted by the Centers for Disease Control and Prevention (CDC, USA) indicated that more than 94,000 people developed life-threatening infections caused by MRSA, and about 19,000 people died due to nocosomial MRSA infections.
At present, MDR diseases are among the most common causes of premature mortality all over the world. Therefore, there is a strong need in resource limited countries, like Pakistan, to review the utility of conventional antibiotics for the management of skin and soft tissue infections, caused by MRSA (Idrees et al., 2009) and to resume research globally in the field of multi-drug resistant infections with innovative approaches.
According to research, 35% MRSA is present in Pakistan. The Central Laboratory could only isolate 792 (91%) live Staphylococcus aureus out of a total of 875 isolates received, from which 332 (42%) were identified as MRSA. The prevalence of MRSA among cities differs with the highest being from Lahore (61%), (57.5%) in Karachi, Rawalpindi/Islamabad having (46%) and (36%) in Peshawar while Sukkur had only 2% MRSA (Sattar et al., 2011; Butt, et al., 2004).
Reported MDR inhibitor 5′-methoxyhydnocarpin (5′-MHC) was isolated from berberine which is produced by Berberis plants (Lewis et al., 2001). Reserpine, an alkaloid from Rauwolfia vomitoria root bark is a well-known bacterial efflux inhibitor against mammalian and for gram-positive organism as well. Reserpine, has activity against one of the Staphylococcus aureus pump's NorA, which contributes to fluoroquinolone resistance in clinical isolates (Mullin et al., 2004). The most common mechanism of resistance in bacteria includes the efflux pumps capable of excreting out a wide range of antibiotics and xenobiotics (Nelson et al., 2002).
The five major mechanisms of antimicrobial resistance include, (i) alterations in the site of action (Coates et al., 2002) (ii) the steps targeted for inhibition can be by-passed. (iii) the intracellular concentration of the drug is reduced (Coates et al., 2002), (iv) inactivation of the antibiotics, and (v) the overproduction of target enzymes (Wright et al., 2005). These mechanisms are mediated by mutation resulted both by horizontal and vertical gene transfer.
There are three main approaches to meet the challenge associated with growing antibiotics resistance:                a. Discovery of new antibiotics, both from natural and synthetic sources.        b. Modifications in the structures of existing antibiotics to synthesize new analogues with enhanced antibiotic properties, and        c. Discovery of “helper” molecules, which help the existing antibiotics to act more effectively by reversing the resistance mechanisms.        
Among them, the third approach has special significance as it addresses the microbial resistance as the core, i.e., molecular level, and increases the life span of existing antibiotics. These helper molecules possibly can block the efflux pumps, depolarizes the membrane potential, revert the resistance by increasing the susceptibility of already ineffective drugs, and induced ROS production in resistant microorganisms. During the current study we discovered aflavonoid, isolated from genus Morus inesozygia Stapf., as highly active and reproducible inhibitors against all tested strains of S. aureus. Morus inesozygia (Moraceae) is a shrub from the tropical and subtropical regions of the world. Stems and the leaves of the plant are used to treat different diseases such as syphilis, dermatitis, rheumatism, asthenias, fever and malaria (Berhaut, 1979, Burkill, 1997). Methanolic extract and isolated compounds from Morus inesozygia are reported to have antimicrobial (Kuete et al., 2009) and antioxidant activities (Kapche et al., 2009). Some compounds, isolated from the leaves of Morus mesozygia, have exhibited inhibitory activity against phosphodiestearse 1 enzyme (Fozing et al., 2011). However, use of any of these compounds has never been reported in treating MDR infections based on their ability to reverse the drug resistance and to provide a surprising. synergism with antibiotics traditionally used to treat infections from Staph aureus. The description of the source of the isolated compounds is not relevant to the invention as any source yielding these compounds would be sufficient for the purpose of this invention.